Re-evaluation of Donor-specific Anti-HLA Alloantibodies Immunoassay After Organ Transplantation, From Antigen Level to Epitope Level (ACORG-HLA)
Re-evaluation of Donor-specific Anti-HLA Alloantibodies Immunoassay After Organ Transplantation, From Antigen Level to Epitope Level: a Track to Improve Organ Allocation
Transplantation is the only treatment for end-stage organ dysfunction, with dialysis for the kidney. However, donor / recipient (D / R) tissue incompatibility accounts for the majority of long-term graft losses, through the development of serum-specific donor antibodies (DSA) to human leukocyte antigens (HLA) of donor, with a prevalence of about 10% at 2 years and 20% at 5 years.
DSA immunization is very often directed against one or a few of the donor's incompatible antigens, suggesting that epitopes (and antigens) are not all equally immunogenic. Identifying HLA epitopes that cause the most and the least immunization would help refine the graft distribution to better manage a limited resource by defining the D / R combinations to avoid or promote. Since the immunogenicity of an HLA epitope depends on the HLA of the recipient given the properties of the epitopes mentioned above, a very large cohort is needed to understand this question. To do so, it is necessary to redo these typings with a method exploring all the genes (add DQA1, DRB3 / 4/5, DPB1 and DPA1) when this has not been done after the graft as part of the standard care. This has become possible since 3 years by DNA sequencing called "new generation" (or NGS), a method that is supplanting all others for the medical care of patients in transplantation.
This study is a retrospective cohort study with 5-year follow-up. The investigators' main objective is to evaluate the predictive value of the number of mismatched HLA epitopes for the development of DSA anti-HLA de novo at 2 years. The investigators' secondary objectives are to evaluate this parameter at 5 and 8 years to determine which epitope mismatches should be favored / avoided in the future.
研究概览
研究类型
注册 (预期的)
联系人和位置
学习联系方式
- 姓名:Jean-Luc TAUPIN, Pr
- 电话号码:+331 42 49 90 81
- 邮箱:jean-luc.taupin@aphp.fr
研究联系人备份
- 姓名:Sylvie Chevret, Pr
- 电话号码:+33142499742 +33142499742
- 邮箱:sylvie.chevret@paris7.jussieu.fr
参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
取样方法
研究人群
描述
Inclusion Criteria:
- patients (adults and children)
- patients recipients in France from 2008 to 2015 of a first kidney transplant / heart / lung / liver donor living or deceased, non-immunized anti-HLA before the transplant
- patients having preserved their graft > 2 years
- having agreed to the use for research purposes in transplantation of the remains of the DNA and serum samples taken as part of the care of which the remains are available
Exclusion Criteria:
- no inclusion if one of the inclusion criteria is not met
学习计划
研究是如何设计的?
设计细节
研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
---|---|---|
Proportion of serum-specific donor antibodies (DSA)
大体时间:at 2 years after organ transplantation
|
Proportion of serum-specific donor antibodies (DSA) regarding epitope mismatches
|
at 2 years after organ transplantation
|
次要结果测量
结果测量 |
大体时间 |
---|---|
Proportion of dnDSA anti-HLA
大体时间:at 2 years after organ transplantation
|
at 2 years after organ transplantation
|
Proportion of dnDSA anti-HLA
大体时间:at 5 years after organ transplantation
|
at 5 years after organ transplantation
|
Proportion of dnDSA anti-HLA
大体时间:at 8 years after organ transplantation
|
at 8 years after organ transplantation
|
Proportion of non-DSA anti-HLA antibodies
大体时间:at 2 years after organ transplantation
|
at 2 years after organ transplantation
|
Proportion of non-DSA anti-HLA antibodies
大体时间:at 5 years after organ transplantation
|
at 5 years after organ transplantation
|
Proportion of non-DSA anti-HLA antibodies
大体时间:at 8 years after organ transplantation
|
at 8 years after organ transplantation
|
Proportion of both total and HLA class I or class II dnDSA by HLA locus (A, B, C, DRB1, DRB3 / 4/5, DQB1, DQA1, DPB1, DPA1) , by HLA antigen, by epitope, for all types of organs and by organ type
大体时间:at 2 years after organ transplantation
|
at 2 years after organ transplantation
|
Proportion of both total and HLA class I or class II dnDSA by HLA locus (A, B, C, DRB1, DRB3 / 4/5, DQB1, DQA1, DPB1, DPA1) , by HLA antigen, by epitope, for all types of organs and by organ type
大体时间:at 5 years after organ transplantation
|
at 5 years after organ transplantation
|
Proportion of both total and HLA class I or class II dnDSA by HLA locus (A, B, C, DRB1, DRB3 / 4/5, DQB1, DQA1, DPB1, DPA1) , by HLA antigen, by epitope, for all types of organs and by organ type
大体时间:at 8 years after organ transplantation
|
at 8 years after organ transplantation
|
Number of dnDSA anti-HLA both total and by HLA class (class I versus class II), by HLA locus (A, B, C, DRB1, DRB3 / 4/5, DQB1, DQA1, DPB1, DPA1), by HLA antigen, for all organ types and organ type
大体时间:at 2 years after organ transplantation
|
at 2 years after organ transplantation
|
Number of dnDSA anti-HLA both total and by HLA class (class I versus class II), by HLA locus (A, B, C, DRB1, DRB3 / 4/5, DQB1, DQA1, DPB1, DPA1), by HLA antigen, for all organ types and organ type
大体时间:at 5 years after organ transplantation
|
at 5 years after organ transplantation
|
Number of dnDSA anti-HLA both total and by HLA class (class I versus class II), by HLA locus (A, B, C, DRB1, DRB3 / 4/5, DQB1, DQA1, DPB1, DPA1), by HLA antigen, for all organ types and organ type
大体时间:at 8 years after organ transplantation
|
at 8 years after organ transplantation
|
Distribution of anti-HLA dnDSA by targeted epitope and antigen (to define immunodominant and non-immunodominant epitopes and antigens), both total and by HLA class (class I versus class II), by HLA locus for all types of organs and organ type
大体时间:at 2 years after organ transplantation
|
at 2 years after organ transplantation
|
Distribution of anti-HLA dnDSA by targeted epitope and antigen (to define immunodominant and non-immunodominant epitopes and antigens), both total and by HLA class (class I versus class II), by HLA locus for all types of organs and organ type
大体时间:at 5 years after organ transplantation
|
at 5 years after organ transplantation
|
Distribution of anti-HLA dnDSA by targeted epitope and antigen (to define immunodominant and non-immunodominant epitopes and antigens), both total and by HLA class (class I versus class II), by HLA locus for all types of organs and organ type
大体时间:at 8 years after organ transplantation
|
at 8 years after organ transplantation
|
Distribution of strength anti-HLA dnDSA measured by mean fluorescence intensity to identify the immunodominant DSA, both global and by class, by HLA locus by HLA antigen, by epitope, for all types of organs and organ type
大体时间:at 2 years after organ transplantation
|
at 2 years after organ transplantation
|
Distribution of strength anti-HLA dnDSA measured by mean fluorescence intensity to identify the immunodominant DSA, both global and by class, by HLA locus by HLA antigen, by epitope, for all types of organs and organ type
大体时间:at 5 years after organ transplantation
|
at 5 years after organ transplantation
|
Distribution of strength anti-HLA dnDSA measured by mean fluorescence intensity to identify the immunodominant DSA, both global and by class, by HLA locus by HLA antigen, by epitope, for all types of organs and organ type
大体时间:at 8 years after organ transplantation
|
at 8 years after organ transplantation
|
Strength in mean fluorescence intensity of dnDSA anti-HLA de novo specific epitopes of epitopes DQbeta, DQalpha and composites (DQbeta + DQalpha) by antigen DQ
大体时间:at 2 years after organ transplantation
|
at 2 years after organ transplantation
|
Strength in mean fluorescence intensity of dnDSA anti-HLA de novo specific epitopes of epitopes DQbeta, DQalpha and composites (DQbeta + DQalpha) by antigen DQ
大体时间:at 5 years after organ transplantation
|
at 5 years after organ transplantation
|
Strength in mean fluorescence intensity of dnDSA anti-HLA de novo specific epitopes of epitopes DQbeta, DQalpha and composites (DQbeta + DQalpha) by antigen DQ
大体时间:at 8 years after organ transplantation
|
at 8 years after organ transplantation
|
Survival of the graft
大体时间:at 5 years after organ transplantation
|
at 5 years after organ transplantation
|
Survival of the graft
大体时间:at 8 years after organ transplantation
|
at 8 years after organ transplantation
|
Overall survival
大体时间:at 5 years after organ transplantation
|
at 5 years after organ transplantation
|
Overall survival
大体时间:at 8 years after organ transplantation
|
at 8 years after organ transplantation
|
合作者和调查者
研究记录日期
研究主要日期
学习开始 (预期的)
初级完成 (预期的)
研究完成 (预期的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
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其他研究编号
- NI16035HLJ
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